New & Noteworthy

C-Circles, an ALT Plan for Telomere Restoration

February 18, 2022

The telomerase ribonucleoprotein complex is the primary means by which yeast cells maintain telomeres. However, it turns out that cells lacking functional telomerase have a backup plan to restore telomere length by “alternative lengthening of telomeres” (ALT). ALT employs recombination via extrachromosomal telomere elements called C-circles. In a process for which the reasons remain unclear, C-circles get paired with eroded telomeres at the nuclear pore complex on the nuclear membrane. This pairing requires the SAGA/TREX2 complex and, once paired, the recombination between C-circles and telomeres appears to be effected by Rad59p, the paralog of Rad52p.

Model of type II telomere recombination that relies on telomeric circles, from Aguilera et al.

This interesting model is described in a recent paper in The EMBO Journal, in which Aguilera et al. adapt a method developed in human cancer studies to detect ALT and C-circles in yeast. In humans, ~10% of cancers depend on ALT for unchecked growth. In yeast, cells with ALT were able to be detected as survivors among telomerase mutant (est2∆) cells.

As other types of extrachromosomal DNA circles were previously reported to associate with the nuclear pore complex, the authors addressed the possibility that C-circles bind the NPC and demonstrated it clearly. They also showed the circles interact with the SAGA/TREX2 complex, which favors telomere recombination.

The novel finding that ALT in yeast so closely mirrors that of some human cancer cells is a boon to study of these cancers. The ability to develop ALT inhibitors in yeast would provide a new set of potential anticancer therapies, making this an ideal model system.

Categories: Research Spotlight

Tags: cancer , cell aging , Saccharomyces cerevisiae , senescence , telomeres , yeast model for human disease